Project Summary/Abstract Cardiovascular disease (CVD) claims more lives and costs more than any other diagnostic group in the USA. Cardiac magnetic resonance (CMR) is a non-invasive imaging tool that provides the most accurate and comprehensive assessment of the cardiovascular system, yet its role in clinical cardiology remains limited. A major impediment to wider usage of CMR is the inefficient acquisition that makes CMR exams excessively long, often lasting for more than an hour; this diminishes its efficiency and cost effectiveness relative to other modalities. The current paradigm offers either a prolonged segmented acquisition that requires regular cardiac rhythm and multiple breath-holds or a fallback option of real-time, free-breathing acquisition with degraded spatial and temporal resolutions that are below the Society for Cardiac Magnetic Resonance guidelines. The long-term goal of this investigation is to improve the diagnosis and evaluation of cardiovascular disease by transforming the existing segmented CMR acquisition into a more efficient protocol. The new paradigm will (i) eliminate the need to breath-hold, (ii) be effective in patients with arrhythmia, (iii) simplify the acquisition protocol, (iv) reduce the scan time, (v) provide whole-heart coverage, and (vi) enable spatial and temporal resolutions that rival the resolutions provided by segmented breath-held acquisition. In the last two decades, MRI technology has evolved rapidly. More recently, the combination of parallel MR imaging (pMRI) and compressive sensing (CS) recovery has been featured in numerous research studies and has delivered unprecedented acceleration. While pMRI has been adopted by the MRI industry and is available on almost all clinical platforms, CS recovery is still a long way away from routine clinical use. To bring CS recovery to clinical realm, there are a number of challenges that need to be addressed, including the well- recognized issues of long computation times and tuning parameters that require case-by-case adjustment. In this work, we will develop and validate a versatile CS recovery method, called sparsity adaptive composite recovery (SCoRe), that provides unmatched acceleration by exploiting sparsity across multiple representations. More importantly, SCoRe provides a data-driven tuning of all free parameters and thus eliminates the need to hand-tune regularization weights. Also, SCoRe is amenable to fast algorithms, and we expect the SCoRe-based image recovery to take only seconds on a GPU-based computing environment. We hypothesize that the proposed advances in data acquisition and processing will yield a new CMR protocol that is faster, easier for both patient and operator, and reliable over a broader spectrum of patients. We expect to achieve this objective by providing the necessary improvements in image quality (Aim 1), by reconstructing images in times suitable for clinical use (Aim 2), by validating the performance of the methods (Aim 3), and by demonstrating the effectiveness and efficiency of this new approach in a clinical trial (Aim 4).